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Biomedical subjects

M B Brown

Publications and source records attributed to M B Brown.

At least 73 records · Page 4Linked to original sources
PubMed1997

Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine.

Interpatient differences in the oral clearance of cyclosporine (INN, ciclosporin) have been partially attributed to variation in the activity of a single liver enzyme termed CYP3A4. Recently it has been shown that small bowel also contains CYP3A4, as well as P-glycoprotein, a protein able to transport cyclosporine. To assess the importance of these intestinal proteins, the oral pharmacokinetics of cyclosporine were measured in 25 kidney transplant recipients who each had their liver CYP3A4 activity quantitated by the intravenous [14C-N-methyl]-erythromycin breath test and who underwent small bowel biopsy for measurement of CYP3A4 and P-glycoprotein. Forward multiple regression revealed that 56% (i.e., r2 = 0.56) and 17% of the variability in apparent oral clearance [log (dose/area under the curve)] were accounted for by variation in liver CYP3A4 activity (p < 0.0001) and intestinal P-glycoprotein concentration (p = 0.0059), respectively. For peak blood concentration, liver CYP3A4 activity accounted for 32% (p = 0.0002) and P-glycoprotein accounted for an additional 30% (p = 0.0024) of the variability. Intestinal levels of CYP3A4, which varied tenfold, did not appear to influence any cyclosporine pharmacokinetic parameter examined. We conclude that intestinal P-glycoprotein plays a significant role in the first-pass elimination of cyclosporine, presumably by being a rate-limiting step in absorption. Drug interactions with cyclosporine previously ascribed to intestinal CYP3A4 may instead be mediated by interactions with intestinal P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A median-based test under informative dropout: the one-sample case.

We consider a clinical trial in which the outcome can be assessed by a continuous measure and where dropouts tend to have poorer efficacy than completers. When each subject can act as his/her own control, efficacy is measured by the difference between the outcome measurements at two times. When all subjects complete the protocol, a paired t-test can be used to test for a treatment effect, i.e., whether or not the mean difference is zero. When a patient does not return for the final evaluation, a measure of efficacy cannot be computed for that subject. Often, data from dropouts are ignored and only the observed pairs are used to analyze the data. When the reason for dropping out is not random, the result may be misleading. In this paper, we assume that (1) the distribution of the measure of efficacy (i.e., the change between two outcome measurements) is Gaussian, (2) dropouts would have worse efficacy than the median if they were observed, and (3) the dropout rate is less than 50%. We propose a median-based t-like statistic using the sample median in place of the sample mean. The variance of the median is estimated using only data from the complete half-sample, i.e., the half-sample with better efficacy. Simulations under five patterns of dropouts are performed to compare the proposed statistic with the paired t-test. The results show that the median-based statistic provides a conservative bound for the test of significance of the treatment. In contrast, because the paired t-test does not preserve its level of significance, except when the dropout mechanism is uniform, the paired t-test should not be used for trials in which dropouts tend to have poorer efficacy than completers.

Bias↗
PubMed1997

Mycoplasma crocodyli sp. nov., a new species from crocodiles.

Organisms with the typical characteristics of mycoplasmas were isolated from joints and lungs of crocodiles. The results of growth inhibition tests and immunobinding assays showed that the 24 mycoplasma strains isolated were identical and distinct from previously described Mycoplasma, Entomoplasma, Mesoplasma, and Acholeplasma species. These organisms represent a new species, for which the name Mycoplasma crocodyli is proposed. M. crocodyli ferments glucose and maltose, does not produce films and spots, does not hydrolyze arginine, esculin, and urea, reduces tetrazolium chloride, and possesses phosphatase activity. It lyses and adsorbs bovine, ovine, and rabbit erythrocytes. Cholesterol or serum is required for growth. The optimum growth temperature is 37 degrees C. The G + C content of the DNA is 27.6 mol%. This organism causes exudative polyarthritis in crocodiles. The type strain of M. crocodyli is strain MP145 (= ATCC 51981).

Alligators and Crocodiles↗
PubMed1997

Relationship between clinical signs of upper respiratory tract disease and antibodies to Mycoplasma agassizii in desert tortoises from Nevada.

Plasma samples collected in 1990 from free-ranging desert tortoises (Gopherus agassizii) with and without clinical signs of upper respiratory tract disease (URTD) from Las Vegas Valley, Clark County, Nevada (USA), were tested by enzyme-linked immunosorbent assay (ELISA) for antibodies to Mycoplasma agassizii, a causative agent of URTD. The relationship between clinical signs and ELISA test results was evaluated. Of the 144 tortoises tested, 45 (31%) had clinical signs while 72 (50%) were seropositive. Presence of clinical signs of URTD was positively related to positive ELISA results (P < 0.0001) regardless of sex or age of the animal. Eighty-four percent of animals with clinical signs tested seropositive. Mucous nasal discharge, the most severe and obvious of the clinical signs, was highly predictive for exposure to M. agassizii based on the ELISA. Ninety-three percent of tortoises with mucous nasal discharge tested seropositive. Serologic testing for M. agassizii antibodies supported clinical signs as useful indicators of URTD, but it also detected potential subclinical infection in 34 (34%) of 99 animals without clinical signs.

Animals↗
PubMed1997

The use of polyethylene glycol (PEG) to enhance the adsorption of autoantibodies.

The use of polyethylene glycol (PEG) to enhance the adsorption of warm autoantibodies on red blood cells (RBCs) was evaluated in our laboratory in an effort to reduce the time and cost associated with routine differential adsorptions. Sera from 19 patients with warm autoantibodies were tested. Fourteen of these sera contained alloantibodies or additional autoantibody specificities underlying the dominant autoantibody. The sera were differentially adsorbed using equal volumes of serum, reagent RBCs, and PEG for 15 minutes at 37 degrees C. The PEG/serum mixture was harvested and used for testing. Six drops of the PEG/serum mixture were tested against reagent RBCs for 15 minutes at 37 degrees C. An antiglobulin test was then performed using anti-IgG. The PEG adsorption technique took a total of 10 hours to completely eliminate autoantibody reactivity in all 19 samples. The reference method required a total of 59.5 hours to adsorb the autoantibodies in all 19 samples. Two weak alloantibody specificities (anti-K, anti-Jkb), known to be present in the serum, were not detected in the PEG tests. Four specificities were weaker with the PEG adsorbed serum. All other alloantibody specificities (13) were detected with equal or greater strength in the PEG adsorbed serum. The use of PEG to enhance the adsorption of autoantibodies should be considered as an option to reduce the time and cost of labor-intensive differential adsorptions. Laboratories should be cautioned that weak alloantibodies may not be detected using this method.

Journal Article↗
PubMed1996

Frequency of median mononeuropathy in patients with mild diabetic neuropathy in the early diabetes intervention trial (EDIT). Tolrestat Study Group For Edit (Early Diabetes Intervention Trial)

We used electrophysiologic criteria to identify median mononeuropathy (MM) at the nondominant wrist among 414 patients enrolled in a multicenter study of patients with mild diabetic neuropathy according to consensus recommendations. Patients with absent sural or peroneal responses or greater than mild symptoms of carpal tunnel syndrome were ineligible. Ninety-five of 414 participants (23%) fulfilled criteria for MM, independent of diabetes type. Patients with MM had a longer duration of diabetes than remaining patients, independent of age, and patients with MM and type II diabetes were more likely to be female (34% vs. 19%; P = 0.008), shorter (165.7 vs. 172.7 cm; P = 0.001), and have a higher body mass index (32.5 vs. 29.1; P = 0.0008) than remaining type II patients. Sural or peroneal conduction abnormalities did not influence the frequency of MM. These results suggest that patients with diabetic neuropathy require special consideration with regard to the evaluation of suspected carpel tunnel syndrome.

Adult↗
PubMed1996

A perioperative elective for college credit.

The authors developed a collaborative perioperative elective course between the Veterans Affairs Medical Center, Louisville, and Indiana University Southeast, New Albany. The course is for students studying for bachelor of science degrees in nursing and is offered as a four-hour elective. The course allows nursing students to participate more in surgical procedures; learn the proper use, care, and cleaning of surgical instruments; and learn nursing theory. Students' and staff members' responses have been favorable.

Curriculum↗
PubMed1996

The role of Mycoplasma species and Ureaplasma species in feline lower urinary tract disease.

The cause of feline lower urinary tract disease (FLUTD) is frequently difficult to determine and may be multifactorial. A controlled cohort study was performed to examine the role of Mycoplasma species and Ureaplasma species in FLUTD. Based on culture and serologic criteria, these microorganisms did not appear to be involved in the group of cats studied. At this time, there is no evidence to implicate Mycoplasma species and Ureaplasma species in FLUTD.

Animals↗
PubMed1996

An in-vitro study of the effect of hydrocolloid patch occlusion on the penetration of triamcinolone acetonide through skin in man.

The aim of this study was to evaluate the effect of occlusion using hydrocolloid-containing patches on in-vitro triamcinolone acetonide (TACA) penetration of the epidermis while monitoring the uptake of water by the patches as a result of transepidermal water loss. The hydrocolloid patches were a laminate of a pressure-sensitive hydrophobic adhesive (containing a dispersion of 39% of either pectin or carmellose sodium) and a polyethylene film. The diffusion of a representative corticosteroid (TACA) through isolated epidermal sheet was shown to depend on the site from which the skin was removed. The two patch-types exhibited markedly different hydration rates when applied to the membranes. For example, after 96 h the carmellose sodium patch showed ten times the weight increase of the pectin patch. Epidermal diffusion rates were, however, similar, both showing a 3-4-fold enhancement over unoccluded conditions. The increase in TACA diffusion with the patches can be explained by the increase in skin hydration that occurs during occlusion. Despite the large differences in transepidermal water transfer through the epidermal membranes with the two types of hydrocolloid patch, however, this level of stratum corneum hydration was apparently similar. As the rate of diffusion was also independent of hydrocolloid patch component, it seems possible that the hydrophobic component of the patch matrix may also influence the level of skin hydration and consequent drug diffusion.

Adult↗
PubMed1996

Experimental genital mycoplasmosis: time of infection influences pregnancy outcome.

Genital infection of rats with Mycoplasma pulmonis causes adverse pregnancy outcome and can result in in utero spread of infection to the fetus. The current study was designed to determine whether the stage of pregnancy when infection occurs influences pregnancy outcome. Rats were inoculated with 3 X 10(7) CFU of M. pulmonis at 10 days prior to breeding (-10) or at gestational day (gd) 11 or 14 and were necropsied at gd 11, 14, or 18 or within 24 h of parturition (term). Control rats received sterile broth. M. pulmonis was isolated from the placenta, amniotic fluid, or fetal tissues only from rats infected prior to breeding (P < 0.001). All infected rats had significantly more loss of pups than did control rats (P < 0.006), but rats infected prior to breeding or at the beginning of the third trimester (gd 14) were much more likely to have fetal losses. Rats infected in the early second trimester after implantation (gd 11) did not experience severe losses. Litter sizes, total litter weight, and individual pup weight from all infected rats, regardless of gestational stage when infected, were significantly smaller than those of control rats (P < 0.001). On the basis of the results of this study, we conclude that the time of infection plays a major role in determination of pregnancy outcome and spread of infection from the genital tract to the respiratory tract.

Animals↗
PubMed1996

Nerve conduction measures in mild diabetic neuropathy in the Early Diabetes Intervention Trial: the effects of age, sex, type of diabetes, disease duration, and anthropometric factors. Tolrestat Study Group for the Early Diabetes Intervention Trial.

We evaluated nerve conduction measures at baseline from 429 patients enrolled in a multicenter diabetic neuropathy study. We defined neuropathy by using recently proposed recommendations but included only patients who had measurable sural and peroneal responses and quantitative vibration thresholds. Patients with type II diabetes were older than type I patients (54.5 versus 39.1 years), were heavier (body mass index [BMI] of 30.9 versus 25.5 kg/m2, and in general had lower evoked amplitudes. The effects of diabetes type upon nerve conduction measures disappeared when age and BMI were included in regression models. The men had lower amplitudes and conduction velocities and longer latencies than the women. The effect of gender was greatly reduced when height was included in the regression models, but gender continued to be a significant predictor of median sensory amplitude, most conduction velocities, and most latencies in these models. The relationships between nerve conduction measures and age, sex, and anthropometric factors were similar for patients with type II, but not those with type I, diabetes to the relationships reported for normal subjects. This may be a result of greater homogeneity with respect to degree of neuropathy for type II patients than for type I patients. These findings are important in designing and interpreting clinical studies of diabetic neuropathy.

Adult↗
PubMed1996

Isolation of Mycoplasma felis from a serval (Felis serval) with severe respiratory disease.

We report cytologic observations and isolation of Mycoplasma felis in September 1992 from the lower respiratory tract of a 3-week-old captive serval (Felis serval) cub with pneumonia, in Florida (USA). Septic, neutrophilic inflammation with a large, monomorphic population of unique, pleomorphic, intracellular and extracellular rods was diagnosed from a transtracheal wash. Mycoplasma felis was the only bacterium isolated in significant numbers from the transtracheal wash.

Animals↗
PubMed1996

A flexible model for human circadian rhythms.

Many hormones and other physiological processes vary in a circadian pattern. Although a sine/cosine function can be used to model these patterns, this functional form is not appropriate when there is asymmetry between the peak and nadir phases. In this paper we describe a semiparametric periodic spline function that can be fit to circadian rhythms. The model includes both phase and amplitude so that the time and the magnitude of the peak or nadir can be estimated. We also describe tests of fit for components in the model. Data from an experiment to study immunological responses in humans are used to demonstrate the methods.

Adrenocorticotropic Hormone↗
PubMed1996

Adolescents becoming adults: attributes for adulthood.

The research literature identifying the end of adolescence and the onset of adulthood has focused on event-related factors (e.g., marriage, occupation), while ignoring cognitive-related factors (e.g., responsibility for one's self and making decisions). This study addresses both realms. Adolescents (N = 113, M age = 16.5 years) were surveyed to determine what they believed were the most important attributes for becoming adults, and at what age their adulthood began. The sample perceived that adult status occurred at a mean age of 17.4 years (SD = 2.55) with 78.8% of the youth reporting that they were "adults." The majority of the sample identified cognitive factors as indicators of adulthood. Further analyses indicated that respondents who perceived that adulthood occurred at younger ages had higher levels of self-esteem. Implications of the consequences of adulthood attributes and beliefs for current and later life adjustment are discussed.

Adolescent↗
PubMed1995

A comparison of methods that characterize pulses in a time series.

There is general recognition that some glands secrete hormones primarily as a series of pulses. One can generally classify the proposed methods of pulse identification and characterization as either (i) criterion-based, that is, they use a criterion such as a test statistic to identify a rise and/or fall in hormone level within a moving window, or (ii) model-based, that is, they specify a statistical model for the time-varying portion of the signal and estimate its parameters. Using simulated data, we compare and contrast seven criterion-based methods and three model-based methods. The model-based methods perform better in estimating the parameters of interest; they are most effective with the sampling rate chosen so that there are 3-5 samples taken during the half-life of the hormone. At higher sampling rates the methods may overidentify pulses (false positives) and at lower sampling rates they may miss pulses (false negatives), both of which lead to biased estimates for the parameters of the signal.

Bias↗
PubMed1995

An investigation of the use of nile red as a long-wavelength fluorescent probe for the study of alpha 1-acid glycoprotein-drug interactions.

Spectrofluorimetry in the long-wavelength region of the electromagnetic spectrum (600-1000 nm) is a fairly recent development in photoluminescence spectroscopy, which has numerous advantages over measurements in the more conventional ultraviolet and visible spectral region. 9-Diethylamino-5H-benzophenoxazine-5-one (Nile Red) is an unchanged, hydrophobic molecule, and long-wavelength fluorescence of which is strongly influenced by the polarity of its environment. When Nile Red was added to solutions of alpha 1-acid glycoprotein (Orosomucoid. OMD), it showed an enhancement in fluorescence intensity and a shift to blue in emission wavelength, suggesting it was binding hydrophobically to a non-polar site on the protein. The association constant (12,261,000 +/- 900,000 M-1) and number of binding sites (0.746 +/- 0.044) were calculated for the probe. Upon addition of both acidic and basic drugs, the Nile Red fluorescence reverted to its unbound form, indicating that OMD probably has one high-affinity, wide and flexible binding area for such drugs. Possible enantiomeric selectivity was shown with ephedrine, and the association constant determined for a racemic mixture of propranolol was found to be comparable to other values obtained with alternative, more conventional techniques.

Buffers↗
PubMed1995

Taxonomic analysis of the tortoise mycoplasmas Mycoplasma agassizii and Mycoplasma testudinis by 16S rRNA gene sequence comparison.

The nucleotide sequences of the 16S rRNA genes of two mycoplasmas, Mycoplasma agassizii (proposed sp. nov.) and Mycoplasma testudinis, isolated from tortoises were determined and used for taxonomic comparisons. Signature nucleotide sequence motifs and overall sequence similarities to other mollicutes positioned these mycoplasmas in the M. hyorhinis and M. pneumoniae phylogenetic groups, respectively. A third, previously unrecognized tortoise mycoplasma was detected by 16S rRNA gene amplification and sequence analysis and was positioned in the M. fermentans phylogenetic group. The 16S rRNA gene of Acholeplasma laidlawii was similarly detected in a tortoise isolate, showing that diverse mollicutes can share the same family of reptilian host.

Animals↗